Biology subjects

Menozzi, L.

Publications and source records attributed to Menozzi, L..

4 recordsLinked to original sources

bioRxiv2026

Whole-body Super-resolution Functional and Molecular Imaging with Panoramic Photoacoustic-Ultrasound Tomography

Photoacoustic (PA) and ultrasound (US) imaging provide complementary molecular, functional, and anatomical contrasts. Here, we present a panoramic PA-US imaging platform that integrates multispectral PA computed tomography (PACT) along with reflection-mode and transmission-mode US imaging through a single shared full-ring ultrasound array. We employ an ultrafast planewave transmission scheme in reflection-mode US for power Doppler (PWD) imaging and ultrasound localization microscopy (ULM). Additionally, we use the transmission-mode US to reconstruct a spatially resolved speed of sound (SoS) map that corrects both PA and US reconstruction. Such correction sharpens the resolution of PACT, suppresses the artifacts of PWD, and improves microbubble localization of ULM. Elevational scanning further enables whole-body volumetric imaging with co-registered PA and US contrasts. The integrated system maps photoswitchable DrBphP1-expressing tumors alongside their blood perfusion and oxygenation environment. Applying the platform to monitor unilateral renal ischemia-reperfusion injury, we report that microvascular perfusion and renal oxygenation recover at different rates. Collectively, we demonstrate that the integrated PA-US imaging platform provides a unified framework for multiparametric study of anatomy, perfusion, microvascular flow, oxygenation, and molecular activities.

bioengineering↗

bioRxiv2026

Photoacoustic Fingerprinting for Robust Molecular Imaging

Quantitative molecular imaging in photoacoustics is fundamentally limited by the ill-posed nature of spectral unmixing, where spectral overlap, noise, and unknown fluence introduce bias in conventional inversion-based methods. We introduce photoacoustic fingerprinting (PAF), a framework that reframes spectral unmixing as a fingerprint recognition problem. PAF interprets multispectral signals as high-dimensional fingerprints encoding both molecular composition and measurement distortions. Inspired by magnetic resonance fingerprinting, PAF uses a recurrent neural network trained on synthetic data spanning realistic mixtures, noise levels, and fluence variations to directly infer molecular concentrations from spectral shape. PAF enables accurate and robust quantification in regimes where conventional methods break down, including low signal-to-noise conditions, spectrally correlated mixtures, and unknown fluence distortions. In controlled simulations, PAF consistently outperformed non-negative least squares, with the largest gains observed for spectrally overlapping chromophores such as collagen. In phantom studies, PAF improved molecular specificity by correctly localizing collagen and recovering water contrast despite similar spectral reconstructions. In ex vivo mouse livers, PAF detected lipid accumulation associated with steatosis, and in human arteries, it identified molecular signatures consistent with thrombus and lipid-rich plaque. These results establish PAF as a generalizable framework for label-free molecular imaging and a promising step toward quantitative photoacoustic diagnostics.

biochemistry↗

bioRxiv2026

Serpin-Driven Green Camouflage and NIR Fluorescence in Frogs

Animals have evolved multiple strategies to generate optical traits and coloration. While most amphibians rely on a three-dimensional arrangement of chromatophores in the skin, hundreds of arboreal frog species achieve leaf-like green color through a different mechanism involving reduced pigmentation, subcutaneous biological mirrors, and high concentrations of the blood-derived pigment biliverdin. Although biliverdin is rapidly excreted in most vertebrates, hylid and centrolenid frogs can retain it through the binding to a serpin-family protein (BBS). Here we show that BBSs bind biliverdin with high affinity (Kd < 10 nM), comparable to hormone-receptor interactions. This interaction alters biliverdins spectral signature in ways that resemble those of green-leaf pigments. BBSs from different species exhibit distinct biophysical properties, accounting for interspecific differences in color saturation and hue. Unlike most serpins in vivo, BBS of the glassfrog Teratohyla pulverata is naturally cleaved, yielding a highly thermostable, thermodynamically favored protein, without loss of affinity. Using custom-designed hyperspectral photoacoustic tomography (PAT), we demonstrate that BBS is widely distributed throughout the body, contributing to whole-body color and camouflage. Furthermore, we show that BBSs emit near-infrared (NIR) fluorescence (>700 nm) rendering these frogs fluorescent in a spectral region where biological tissues are largely transparent. Together, BBSs shed light on serpin evolution, protein thermostability, amphibian color diversity, and the development of NIR molecular probes.

biochemistry↗

bioRxiv2024

Advanced deep-tissue imaging and manipulation enabled by biliverdin reductase knockout.

We developed near-infrared (NIR) photoacoustic and fluorescence probes, as well as optogenetic tools from bacteriophytochromes, and enhanced their performance using biliverdin reductase-A knock-out model (Blvra-/-). Blvra-/- elevates endogenous heme-derived biliverdin chromophore for bacteriophytochrome-derived NIR constructs. Consequently, light-controlled transcription with IsPadC-based optogenetic tool improved up to 25-fold compared to wild-type cells, with 100-fold activation in Blvra-/- neurons. In vivo, light-induced insulin production in Blvra-/- reduced blood glucose in diabetes by [~]60%, indicating high potential for optogenetic therapy. Using 3D photoacoustic, ultrasound, and two-photon fluorescence imaging, we overcame depth limitations of recording NIR probes. We achieved simultaneous photoacoustic imaging of DrBphP in neurons and super-resolution ultrasound localization microscopy of blood vessels [~]7 mm deep in the brain, with intact scalp and skull. Two-photon microscopy provided cell-level resolution of miRFP720-expressing neurons [~]2.2 mm deep. Blvra-/- significantly enhances efficacy of biliverdin-dependent NIR systems, making it promising platform for interrogation and manipulation of biological processes.

cell biology↗